November 26, 2013

Cognition, Mood Changes Not Linked To Postmenopausal Estrogen Loss

Decreased estrogen levels after menopause are largely unrelated to changes in cognitive ability and mood, according to a new study led by Stanford University School of Medicine.

The study, published in Proceedings of the National Academy of Sciences (PNAS), found a possible link between levels of progesterone and cognition among younger postmenopausal women, however.

First to investigate associations between sex hormones and cognition in both younger and older postmenopausal women, the study determines whether the hormones affect women differently based on their age and how much time has elapsed since they reached menopause.

Victor Henderson, MD, professor of health research and policy and of neurology and neurological sciences, and his colleagues noted that the findings help clarify the role of hormones in age-related brain disturbances.

Estrogen is the main sex hormone for women, and as such plays a crucial role in a woman's reproductive cycle and overall health. The depletion of ovarian follicles after menopause leads to a permanent reduction in the levels of estradiol (the predominant estrogen before menopause, estrone (the predominant estrogen after) and progesterone (another hormone involved in the menstrual cycle) in a woman's body. Previous studies have examined the association between cognition and hormone concentrations, but the results have been inconsistent.

One theory suggests that the effect of estrogen on cognitive aging might differ depending on when exposure occurs. "Some effects might be more beneficial for younger postmenopausal women closer to the time of menopause than for older postmenopausal women," Henderson said of the so-called "critical-window" hypothesis.

Henderson's team analyzed data on 643 healthy postmenopausal women who were part of the ongoing Early Versus Late Intervention Trial With Estradiol. None of the women, who were between the ages of 41 and 84, were on hormone therapy at the time of the study.

The researchers sorted the women into two categories: those who had gone into menopause less than six years previously, and those who had gone into menopause more than 10 years previously. The participants were given a series of neuropsychological tests designed to gauge their memory and overall cognition, then assessed for depression and measured for levels of estradiol, estrone, progesterone and testosterone.

"We viewed the availability of hormone levels as an opportunity to test one aspect of the critical-window hypothesis — especially since we had two fairly large samples of women," Henderson said.

Henderson and his colleagues hypothesized that higher levels of estradiol would be positively associated with memory performance in women who had experienced menopause more recently, based on the critical-window theory, along with results of past animal studies showing that the timing of estradiol replacement affects memory. They did not expect to see the same results in women who had experienced menopause longer ago.

The findings don't "necessarily mean that estrogens are irrelevant to cognition, since we have no way of measuring estrogen directly at the brain level. But they imply that boosting blood levels of estradiol or estrone — even in younger postmenopausal women — may not have a substantial effect on cognitive skills one way or the other," said Henderson.

The researchers found other hormone levels were unrelated to verbal memory, executive function or overall cognition or mood. They found one exception to this: Higher progesterone levels in younger postmenopausal women were positively associated with better memory and global cognition.

"This finding has not been previously reported and needs to be confirmed," Henderson added.

According to the authors, the study's strengths include "the large sample size for both early and late postmenopausal women, the examination of multiple sex hormones in the same population, and the use of a comprehensive neuropsychological battery that allowed for the assessment of different cognitive domains."